Adolescent and young adult abuse of short-acting MOP-r agonists such as oxycodone is a pressing public health issue. Few preclinical studies have examined how adolescent exposure to oxycodone impacts its effects in the transition to adulthood. Objective To determine in mice how chronic adolescent oxycodone self-administration (SA) affects subsequent oxycodone-induced conditioned place preference (CPP), locomotor activity, and anti-nociception once mice reach early adulthood. Methods Adolescent C57BL/6J male mice (4 weeks old, n = 6–11) and adult mice (10 weeks old, n = 6–10) were surgically implanted with indwelling jugular catheters. Mice then acquired oxycodone self-administration (14 consecutive 2-hr daily sessions; 0.25 mg/kg/infusion) followed by a 14-day drug-free (withdrawal) period in home cage. After the 14-day drug-free period, mice underwent a 10-day oxycodone CPP procedure (0, 1, 3, 10 mg/kg i.p.) or were tested for acute oxycodone-induced anti-nociception in the hot plate assay (3.35, 5, 7.5 mg/kg i.p.). Results Mice that self-administered oxycodone during adolescence exhibited greater oxycodone-induced CPP (at the 3 mg/kg dose) than their yoked saline controls and mice that self-administered oxycodone during adulthood. Oxycodone dose-dependently increased locomotor activity, but sensitization developed only to the 3 mg/kg in the mice that underwent oxycodone self-administration as adolescents. Mice that self-administered oxycodone as adolescents decreased in the anti-nociceptive effects of oxycodone in one dose (5 mg/kg), whereas animals that self-administered oxycodone as adults did not show this effect. Conclusion Chronic adolescent oxycodone self-administration led to increased oxycodone-induced CPP (primarily 1 and 3 mg/kg, i.p.) and reduced antinociceptive effect of oxycodone (5 mg/kg, i.p.) in adulthood.

Background The Differentiator Model predicts that individuals with a positive family history of alcoholism or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. This study tested if subjective perceptions are sensitive to the slope of breath alcohol concentration and if that sensitivity is associated with a family history of alcoholism (FHA) and/or recent drinking history (RDH). Methods Family history positive (FHP, N=27) and family history negative (FHN, N=27) young adult non-dependent drinkers were infused intravenously with alcohol in 2 sessions separated by one week. After 20 minutes, one session had an ascending BrAC (+3.0mg% per min) while the other session had a descending BrAC (−1 mg% per min). The BrAC for both sessions at this point was approximately 60 mg%, referred to as the crossover point. Subjective perceptions of intoxication, high, stimulated, and sedation were sampled frequently, then interpolated to the crossover point. Within-subject differences between ascending and descending responses were examined for associations with FHA and/or RDH. Results Recent moderate drinkers reported increased perceptions of feeling intoxicated (p<0.023) and high (p<0.023) on the ascending slope compared to the descending slope. In contrast, recent light drinkers felt more intoxicated and high on the descending slope. Conclusion Subjective perceptions in young adult social drinkers depend on the slope of the BrAC when examined in association with RDH. These results support the Differentiator Model hypothesis concerning the ascending slope and suggest that moderate alcohol consumers could be at risk for increased alcohol consumption because they feel more intoxicated and high on the ascending slope. Subjects did not feel less sedated on the descending slope, contrary to the Differentiator Model but replicating several previous studies.